Safety and Efficacy Study of GDC-0853 Compared With Placebo and Adalimumab in Participants With Rheumatoid Arthritis (RA)

Phase 2

Completed

Conditions: Rheumatoid Arthritis

Interventions: Drug: GDC-0853
Drug: Adalimumab
Drug: Folic Acid
Drug: MTX
Drug: Placebo

Registration Number: NCT02833350

Lead Sponsor: Genentech, Inc.

Brief Summary: This is a multicenter, Phase II, randomized, double-blind, placebo-controlled, active comparator (Cohort 1 only), parallel-group, dose-ranging study to evaluate the efficacy and safety of GDC-0853 in participants with moderate to severe active RA and an inadequate response to previous methotrexate (MTX) therapy (Cohort 1) or MTX and tumor necrosis factor (TNF) therapy who may have also had exposure to no more than one non-TNF inhibitor biologic (Cohort 2).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 578

Inclusion Criteria

Have a diagnosis of adult-onset RA as defined by the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for RA
RA disease activity by joint counts and laboratory markers of inflammation: greater than or equal to (>=) 6 tender/painful joints on motion (68 joint count) and >= 6 swollen joints (66 joint count) at both screening and Day 1 (randomization)
For MTX-inadequate response (IR) participants: must have had an inadequate response to MTX
For TNF-IR participants: must have had an inadequate response or intolerance to previous treatment with at least 1 and no more than 2 biologic TNF-alpha inhibitors and may have also been exposed to no more than one biologic non-TNF-alpha inhibitor
High sensitivity C-reactive protein of >= 0.400 milligrams per deciliter (mg/dL) for Cohort 1 and >= 0.650 mg/dL for Cohort 2 at screening

Exclusion Criteria

History of or current inflammatory joint disease other than RA or other systemic autoimmune disorder
For MTX-IR participants: History of treatment with any TNF inhibitor, including biosimilar equivalents and history of treatment with biologic non-TNF-alpha inhibitor for RA
For all participants: Previous treatment with cell-depleting therapy including B cell-depleting therapy (e.g., anti-cluster of differentiation 20-directed therapy such as rituximab), tofacitinib, or other Janus kinase inhibitor(s), or alkylating agents
Current treatment with medications that are well known to prolong the QT interval at doses that have a clinically meaningful effect on QT
History of non-gallstone-related pancreatitis or chronic pancreatitis
Evidence of serious uncontrolled concomitant cardiac, neurologic, pulmonary, renal, hepatic, endocrine, metabolic, or gastrointestinal disease
Evidence of chronic and/or active hepatitis B or C
Women who are pregnant, nursing (breast feeding), or intending to become pregnant during the study or within 60 days after completion of the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Placebo	Participants of Cohort 1 will receive GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	GDC-0853	Participants of Cohort 1 will receive GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Placebo	Participants of Cohort 1 will receive GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Placebo	Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Placebo	Participants of Cohort 1 will receive GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Placebo + Adalimumab	Placebo	Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 2: GDC-0853 Placebo	Placebo	Participants of Cohort 2 will receive placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	GDC-0853	Participants of Cohort 1 will receive GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	GDC-0853	Participants of Cohort 1 will receive GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 2: GDC-0853 High Dose	GDC-0853	Participants of Cohort 2 will receive GDC-0853 high dose, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	MTX	Participants of Cohort 1 will receive GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Folic Acid	Participants of Cohort 1 will receive GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Folic Acid	Participants of Cohort 1 will receive GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	MTX	Participants of Cohort 1 will receive GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Folic Acid	Participants of Cohort 1 will receive GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	MTX	Participants of Cohort 1 will receive GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Placebo + Adalimumab	Folic Acid	Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Placebo + Adalimumab	Adalimumab	Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Folic Acid	Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Placebo + Adalimumab	MTX	Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	MTX	Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 2: GDC-0853 High Dose	Folic Acid	Participants of Cohort 2 will receive GDC-0853 high dose, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 2: GDC-0853 Placebo	Folic Acid	Participants of Cohort 2 will receive placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 2: GDC-0853 High Dose	MTX	Participants of Cohort 2 will receive GDC-0853 high dose, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Cohort 2: GDC-0853 Placebo	MTX	Participants of Cohort 2 will receive placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events	Day 1 up to 8 weeks after last dose (up to Week 20)	An Adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE was any experience that suggested a significant hazard, contraindication, side effect or precaution that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 1)	Day 84	ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].

Secondary Outcome Measures

Name	Time	Method
Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])	Days 7, 14, 28, 56, and 84	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Percentage of Participants With DAS Remission	Days 7, 14, 28, 56, and 84	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6
Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Adalimumab (Cohort 1)	Day 84	ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 2)	Day 84	ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response	Days 7, 14, 28, 56, and 84	ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\]
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components	Day 84	The 36-Item Short Form Health Survey (SF-36v2) is a questionnaire used to assess functional health and well-being and consists of eight domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. The SF-36v2 is summarized into Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. The PCS and MCS scores range from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.
Change From Baseline in Swollen Joint Count (66 Joint Count)	Days 7, 14, 28, 56, and 84	Swollen Joint Count: a total of 66 joints will be assessed for swelling. Each joint is assessed for the presence/absence of swelling. 66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement.
Change From Baseline in Patient Global Assessment Score of Arthritis Pain	Days 7, 14, 28, 56, and 84	Participant-assessed arthritis pain was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of arthritis pain (0 mm=none; 100 mm=very severe). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change indicated a decrease in participant-assessed arthritis pain.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	Days 7, 14, 28, 56, and 84	The Stanford Health Assessment Questionnaire disability index is a patient-reported outcome used to assess difficulty in performing activities of daily living. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. To respond to each question, a four-level response with higher scores showing larger functional limitations, was chosen. Scoring is as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. The composite HAQ-DI score is the mean of the eight domain scores and the score ranges from 0 (no functional impairment) to 3 (maximum functional impairment). A negative change from baseline indicates improvement.
Percentage of Participants Meeting the CDAI-based Remission Criteria	Days 7, 14, 28, 56, and 84	Clinical Disease Activity Index is defined as CDAI= : SJC(28) + TJC(28) + PGA + MDG where TJC and SJC are the tender and swollen joint counts from 28 joints, PGA is the patient's global assessment of disease activity (on a 0-10 scale) and MDG is physician global assessment of disease activity (on a 0-10 scale). The cutoff value for CDAI remission is \<=2.8.
Percentage of Participants Meeting the SDAI-based Remission Criteria	Days 7, 14, 28, 56, and 84	The SDAI was the numerical sum of five outcome parameter: SJC and TJC (based on a 28-joint assessment), PGA and MDG (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. The SDAI =\< 3.3 indicates disease remission
Change From Baseline in Patient Assessment Score of Arthritis Pain	Days 7, 14, 28, 56, and 84	Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response	Days 7, 14, 28, 56, and 84	ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])	Days 7, 14, 28, 56, and 84	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])	Days 7, 14, 28, 56, and 84	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR])	Days 7, 14, 28, 56, and 84	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Percentage of Participants With DAS Low Disease Activity	Days 7, 14, 28, 56, and 84	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDAS is defined as DAS28 ≤ 3.2
Change From Baseline in Clinical Disease Activity Index (CDAI)	Baseline, Days 7, 14, 28, 56 and 84	CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest. Negative values indicate improvement/reduction in RA disease activity.
Minimum Observed Plasma Concentration of GDC-0853 at Steady State (Cmin,ss)	Pre-dose (0 hours) up to 10 hours post-dose on Day 28	Cmin is the minimum concentration over the dosing interval at steady state (ss)
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response	Days 7, 14, 28, 56, and 84	ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
Percentage of Participants Meeting the Boolean-based Remission Criteria	Days 7, 14, 28, 56, and 84	Boolean Remission is defined as Tender joint count less than 1, Swollen joint count less than 1, CRP less than 1 mg/dL, patient global assessment less than 1 (on 0 to 10 VAS scale).
Change From Baseline in Simplified Disease Activity Index (SDAI)	Baseline, Days 7, 14, 28, 56 and 84	Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =\< 3.3 indicates disease remission, \> 3.4 to 11 indicates low disease activity, \> 11 to 26 indicates moderate disease activity, and \> 26 indicates high disease activity
Change From Baseline in Tender/Painful Joint Count (68 Joint Count)	Days 7, 14, 28, 56, and 84	Tender Joint Count: a total of 68 joints will be assessed for tenderness. Each joint is assessed for the presence/absence of tenderness. 68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement.
Change From Baseline in Physician's Global Assessment Score of Arthritis	Days 7, 14, 28, 56, and 84	Physician's assessment of participant's disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's assessment of the participant's disease activity (0 mm=very good; 100 mm=very poor). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change from baseline indicated an improvement in physician-assessed disease activity.
Change From Baseline in C-Reactive Protein (CRP) Levels	Days 7, 14, 28, 56, and 84	C-reactive protein is a biological marker of inflammation and is measured in nanograms per milliliter (ng/mL)
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score	Day 84	The FACIT-Fatigue Scale consists of 13 items designed to measure the degree of fatigue experienced by the patient in the previous 7 days. For each question, there are five possible responses: 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit), 4 (very much). A total fatigue score is calculated by summing all items, and possible total scores range from 0 (maximum fatigue) to 52 (no fatigue). A positive change from baseline indicates an improvement in the patient's fatigue (less fatigue).
Area Under the Concentration Time Curve From Time 0 to Time 24 of GDC-0853 at Steady State (AUC0-24,ss)	Pre-dose (0 hours) up to 10 hours post-dose on Day 28	The Pharmacokinetics (PK) evaluation may include, but will not be limited to, plasma GDC-0853 concentrations and population PK model estimated PK exposures (area under the plasma concentration-time curve \[AUC\]. AUC was measured in Nanograms(ng) per millilitre(mL)\*hour (hr)
Maximum Observed Plasma Concentration of GDC-0853 at Steady State (Cmax,ss)	Pre-dose (0 hours) up to 10 hours post-dose on Day 28	Cmax is the maximum (peak) plasma concentration over the dosing interval at steady state (ss)

Trial Locations

Locations (150): Pinnacle Research Group; Llc, Central
🇺🇸
Anniston, Alabama, United States
Medvin Clinical Research
🇺🇸
Covina, California, United States
TriWest Research Associates, LLC
🇺🇸
El Cajon, California, United States
Stanford University School of Medicine
🇺🇸
Stanford, California, United States
ZASA Clinical Research
🇺🇸
Boynton Beach, Florida, United States
Omega Research Consultants
🇺🇸
Orlando, Florida, United States
McIlwain Medical Group
🇺🇸
Tampa, Florida, United States
Clinical Research Center of Reading
🇺🇸
Wyomissing, Pennsylvania, United States
Crossroads Clinical Research, LLC
🇺🇸
Victoria, Texas, United States
Danville Orthopedic Clinic, Inc.; Research Department
🇺🇸
Danville, Virginia, United States
Organizacion Medica de Investigacion
🇦🇷
Buenos Aires, Argentina
Hospital Italiano
🇦🇷
Buenos Aires, Argentina
CIP - Centro Internacional de Pesquisa; Pesquisa Clinica
🇧🇷
Goiânia, GO, Brazil
Centro Mineiro de Pesquisa - CMIP
🇧🇷
Juiz de Fora, MG, Brazil
Edumed - Educação e Saúde SA
🇧🇷
Curitiba, PR, Brazil
Centro de Estudos em Terapias Inovadoras - CETI
🇧🇷
Curtiba, PR, Brazil
CCBR - Synarc Centro de Pesquisa Clinica - RJ
🇧🇷
Rio de Janeiro, RJ, Brazil
Hospital Sao Vicente de Paulo
🇧🇷
Passo Fundo, RS, Brazil
LMK Serviços Médicos S/S
🇧🇷
Porto Alegre, RS, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio Preto
🇧🇷
São José do Rio Preto, SP, Brazil
CAEP - Centro Avancado de Estudos e Pesquisas Ltda.
🇧🇷
Campinas, SP, Brazil
Instituto de Pesquisa Clínica e Medicina Avançada Ltda
🇧🇷
Sao Paulo, SP, Brazil
Faculdade de Medicina do ABC - FMABC
🇧🇷
Santo Andre, SP, Brazil
CPCLIN - Centro de Pesquisas Clínicas Ltda.; Pesquisa Clinica
🇧🇷
São Paulo, SP, Brazil
MHAT Kaspela; EOOD
🇧🇬
Plovdiv, Bulgaria
MC "Synexus - Sofia", EOOD
🇧🇬
Sofia, Bulgaria
Hospital Pablo Tobon Uribe
🇨🇴
Medellin, Colombia
Clinica de Artritis Temprana S.A.
🇨🇴
Cali, Colombia
Chungnam National University Hospital; Department of Internal Medicine (Rheumatology)
🇰🇷
Daejeon, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷
Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Konkuk University Medical Center
🇰🇷
Seoul, Korea, Republic of
Asan Medical Center - Oncology
🇰🇷
Seoul, Korea, Republic of
Ajou University Hospital
🇰🇷
Suwon City, Korea, Republic of
Centro de Investigacion Clínica GRAMEL S.C
🇲🇽
Mexico, Mexico
Centrum Medyczne AMED
🇵🇱
Warszawa, Poland
Wojewódzki Szpital Specjalistyczny we Wrocławiu
🇵🇱
Wrocław, Poland
LLC Medical Sanitary Unit
🇷🇺
Sankt-peterburg, Sankt Petersburg, Russian Federation
SMMIH "Chelyabinsk Regional Clinical Hospital"
🇷🇺
Chelyabinsk, Voronez, Russian Federation
CNI Consultative and Diagnostic Center of Desnianskyi District of Kyiv
🇺🇦
Kyiv, Ukraine
MI of Helathcare Kyiv RCH P.L. Shupy NMA of PGE
🇺🇦
Kyiv, Ukraine
CI City Hospital #7
🇺🇦
Zaporizhzhia, Ukraine
Oleksandrivska Clinical Hospital
🇺🇦
Kyiv, Ukraine
Instituto centenario
🇦🇷
Buenos Aires, Argentina
Arizona Arthritis & Rheumatology Associates, P.C.
🇺🇸
Glendale, Arizona, United States
Advanced Clinical Research
🇺🇸
Meridian, Idaho, United States
Centro de Investigacion en Enfermedades Reumaticas CIER
🇦🇷
Ciudad Autonoma Buenos Aires, Argentina
Expertia S.A- Mautalen Salud e Investigación
🇦🇷
Ciudad Autonoma Buenos Aires, Argentina
Instituto de Investigaciones Clinicas-Mar del Plata
🇦🇷
Buenos Aires, Argentina
CCBR - Buenos Aires - AR; AxisMed SRL
🇦🇷
Ciudad Autonoma Buenos Aires, Argentina
ILAIM-CEOM Inst. Latinoamericano de Inv. Medicas
🇦🇷
Cordoba, Argentina
Centro de Investigaciones Medicas Mar Del Plata
🇦🇷
Mar del Plata, Argentina
APRILLUS
🇦🇷
Buenos Aires, Argentina
Hospital Italiano de La Plata
🇦🇷
La Plata, Argentina
Centro Medico Privado de Reumatologia; Reumathology
🇦🇷
San Miguel, Argentina
Instituto de Investigaciones Clínicas Quilmes
🇦🇷
Quilmes, Argentina
CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
🇦🇷
San Juan, Argentina
MHAT - Dobrich, AD
🇧🇬
Dobrich, Bulgaria
Medizinski Zentrar-1-Sevlievo EOOD
🇧🇬
Sevlievo, Bulgaria
MHAT "Eurohospital" - Plovdiv, OOD
🇧🇬
Plovdiv, Bulgaria
MHAT - Ruse, AD
🇧🇬
Ruse, Bulgaria
MHAT "Hadzhi Dimitar", OOD
🇧🇬
Sliven, Bulgaria
Medical Center Excelsior OOD
🇧🇬
Sofia, Bulgaria
DCC "Alexandrovska", EOOD; Clinic of Neurology
🇧🇬
Sofia, Bulgaria
UMHAT "SofiaMed", OOD
🇧🇬
Sofia, Bulgaria
MHAT Dr. St. Kirkovich, AD
🇧🇬
Stara Zagora, Bulgaria
'New Medical Center' , EOOD
🇧🇬
Vratsa, Bulgaria
Centro de Reumatologia y Ortopedia
🇨🇴
Barranquilla, Colombia
Centro de Investigacion en Reumatologia y Especialdades Medicas SAS. CIREEM
🇨🇴
Bogota, Colombia
Riesgo de Fractura S.A.
🇨🇴
Bogota, Colombia
Fundación Instituto de Reumatología Fernando Chalem
🇨🇴
Bogota, Colombia
Centro de Investigacion en Reumatologia
🇲🇽
Merida, Yucatan, Mexico
Consultorio Medico en Fundacion el Hospitalito de morelos A.C.
🇲🇽
Cuernavaca, Morelos, Mexico
Chonnam National University Hospital
🇰🇷
Gwangju, Korea, Republic of
Consultorio Particular del Dr. Miguel Cortes Hernandez
🇲🇽
Cuernavaca, Mexico
Centro de Investigacion en Enfermedades Reumaticas y Osteoporosis
🇲🇽
Mexicali, Mexico
Policilinica Medica de Queretaro; Rheumatology
🇲🇽
Queretaro, Mexico
Clinical Research Institute
🇲🇽
Tlalnepantla, Mexico
Ai Centrum Medyczne Sp. Z O.O Sp.K.
🇵🇱
Poznan, Poland
TSBIH "Krasnoyarsk Interdistrict Clinical Hospital of Emergency Medical Care n.a. N.S. Karpovich
🇷🇺
Krasnoyarsk, Krasnojarsk, Russian Federation
Unidad de Enfermedades Reumaticas y Cronicodegenerativas
🇲🇽
Torreon, Mexico
Szpital Uniwersytecki; nr 2 im. Dr J. Biziela
🇵🇱
Bydgoszcz, Poland
Medica Pro Familia Spolka Akcyjna Oddzial w Katowicach
🇵🇱
Katowice, Poland
KO-MED Centra Kliniczne Staszow
🇵🇱
Staszow, Poland
Sanavita LLC
🇷🇺
Sankt-peterburg, Sankt Petersburg, Russian Federation
NZOZ OSTEO-MEDIC S.C. Artur Racewicz, Jerzy Supronik
🇵🇱
Bialystok, Poland
Centrum Medyczne Plejady
🇵🇱
Krakow, Poland
CCBR - Lodz - PL
🇵🇱
Lodz, Poland
ETYKA Osrodek Badan Kliniczynch
🇵🇱
Olsztyn, Poland
KO-MED Centra Kliniczne Zamosc
🇵🇱
Zamosc, Poland
SBEI HPE " First Moscow State Medical University n.a. I.M. Sechenov" of the MoH of the RF
🇷🇺
Moscow, Moskovskaja Oblast, Russian Federation
SBEI HPE "Smolensk State Medical University" of the MoH of the RF
🇷🇺
Smolensk, Russian Federation
Siberian State Medical University
🇷🇺
Tomsk, Russian Federation
Institute of Rheumatology
🇷🇸
Belgrade, Serbia
General Hospital Sabac; Department of Urology and Hemodialysis
🇷🇸
Sabac, Serbia
Regional CH Dep of Rheumatology SHEI Ivano-Frankivsk NMU
🇺🇦
Ivano-Frankivsk, KIEV Governorate, Ukraine
Medical Center Medical Clinic Blagomed LLC.
🇺🇦
Kyiv, KIEV Governorate, Ukraine
Federal State Budgetary Scientific Institution Research Institute of Rheumatology V.A. Nasonova
🇷🇺
Moscow, Moskovskaja Oblast, Russian Federation
Center of Family Medicine LC
🇷🇺
Yekaterinburg, Sankt Petersburg, Russian Federation
SBHI of Yaroslavl Region Clinical Hospital #3
🇷🇺
Yaroslavl, Volgograd, Russian Federation
SBIH of Moscow "City Clinical Hospital # 1 n. a. N. I. Pirogov"
🇷🇺
Moscow, Moskovskaja Oblast, Russian Federation
Technologii zdorovia LLC
🇷🇺
Sankt-peterburg, Sankt Petersburg, Russian Federation
Limited Liability Company "Centre of Medical Common Practice"
🇷🇺
Novosibirsk, Russian Federation
SAHI of Kem. "Regional Clinical Hospital for War Veterans"
🇷🇺
Kemerovo, Russian Federation
Practical Medicine
🇷🇺
Moscow, Russian Federation
OOO Family Polyclinic
🇷🇺
Korolev, Moscow Region, Russian Federation
SHI Yaroslavl Regional Clinical Hospital
🇷🇺
Yaroslavl, Russian Federation
Ultramed
🇷🇺
Omsk, Russian Federation
SHI Ulyanovsk Reg Clinical Hospital
🇷🇺
Ulyanovsk, Russian Federation
Territorial Clinical Hospital #2
🇷🇺
Vladivostok, Russian Federation
SBEI HPE "Saratov State Medical University n.a. V. I. Razumovskiy" of the MoH of the RF
🇷🇺
Saratov, Russian Federation
City Hospital 25; Rheumatology
🇷🇺
St. Petersburg, Russian Federation
Pavlov First Saint Petersburg State Medical University
🇷🇺
St. Petersburg, Russian Federation
Military Medical Academy
🇷🇸
Belgrade, Serbia
Lviv Regional Clinical Hospital Dept of Rehmuaatology D. Halytskyi Lviv NMU
🇺🇦
Lviv, KIEV Governorate, Ukraine
GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine
🇺🇦
Kharkiv, Ukraine
Gerontology Institute of the Ukrainian AMS
🇺🇦
Kyiv, Ukraine
Clinical Center Kragujevac
🇷🇸
Kragujevac, Serbia
Institute of Treatment and Rehabilitation "Niska Banja"
🇷🇸
Niska Banja, Serbia
Special hospital for rheumatic diseases Novi Sad
🇷🇸
Novi Sad, Serbia
CI of TRC
🇺🇦
Ternopil, Kherson Governorate, Ukraine
Medical Center OK!Clinic+
🇺🇦
Kyiv, KIEV Governorate, Ukraine
SI NSС M.D. Strazhesko Institute of Cardiology of NAMSU
🇺🇦
Kyiv, KIEV Governorate, Ukraine
Clinic of Modern Rheumatology Revmotsentr LLC
🇺🇦
Kyiv, KIEV Governorate, Ukraine
CH of State Border Service of Ukraine (Military Base 2522); Dept of Therapy, D.Halytskyi Lviv NMU
🇺🇦
Lviv, KIEV Governorate, Ukraine
A.Novak Transcarpathian Regional Clinical Hospital
🇺🇦
Uzhgorod, KIEV Governorate, Ukraine
Railway Transp DCH of HealthCenter Branch of PJSC Ukr Railway Dept of Rheumatology
🇺🇦
Dnipro, Tavria Okruha, Ukraine
Kharkiv MA of PGE of MOHU Ch of Cardiology and Functional Diagnostics
🇺🇦
Kharkiv, Ukraine
Volyn Regional Center of Cardiovascular Pathology and Thrombolysis
🇺🇦
Lutsk, Ukraine
City Hospital #1
🇺🇦
Mykolaiv, Ukraine
M.V. Sklifosovsky Poltava RCH Dept of Rheumatology HSEIU UMSA
🇺🇦
Poltava, Ukraine
Private Small Enterprise Medical Center Pulse
🇺🇦
Vinnytsia, Ukraine
CI Zaporizhzhia Regional Clinical Hospital of ZRC
🇺🇦
Zaporizhzhia, Ukraine
M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU
🇺🇦
Vinnytsia, Ukraine
City Clinical Hospital #9 Dept of Gastrosurgery SI Zaporizhzhia MA of PGE of MoHU
🇺🇦
Zaporizhzhia, Ukraine
NMTH "Tsar Boris III"
🇧🇬
Sofia, Bulgaria
MHAT "Lyulin", EAD
🇧🇬
Sofia, Bulgaria
Medycyna Kliniczna
🇵🇱
Warszawa, Poland
Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)
🇲🇽
Culiacán Rosales, Sinaloa, Mexico
Saint Jude Heritage Medical Grp
🇺🇸
Fullerton, California, United States
RASF-Clinical Research Center
🇺🇸
Boca Raton, Florida, United States
Clinical Research of West Florida
🇺🇸
Clearwater, Florida, United States
InVentiv Health
🇺🇸
Miami, Florida, United States
Institute of Arthritis Research
🇺🇸
Idaho Falls, Idaho, United States
Medication Management
🇺🇸
Greensboro, North Carolina, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Metroplex Clinical Research
🇺🇸
Dallas, Texas, United States
Baylor Research Inst.
🇺🇸
Dallas, Texas, United States
Accurate Clinical Management - VO
🇺🇸
Houston, Texas, United States
Accurate Clinical Research
🇺🇸
Houston, Texas, United States